Elucidation of mechanism of suppressing cancer metastasis by differentiation-inducing factor 1

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07292
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: University of Occupational and Environmental Health, Japan (2022); Kyushu University (2020-2021)
• Principal Investigator: Arioka Masaki 産業医科大学, 医学部, 講師 (20733554)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞接着 / DIF-1 / mTORC1 / 転移 / VCAM-1 / S6K

Outline of Final Research Achievements

We have previously reported that differentiation-inducing factor-1 (DIF-1) exhibits anti-cancer effects in various mammalian cancer cells. In the present study, we tried to identify the mechanism of the anti-metastatic effect of DIF-1 by focusing on the circulating tumor cell adhesion to blood vessels. We found that intragastric administration of DIF-1 prior to cancer cell inoculation via tail vein suppressed lung colony formation in murine pulmonary metastasis model and that DIF-1 significantly inhibited adhesion of cancer cells to human umbilical vein endothelial cells (HUVECs). Although DIF-1 did not affect the expression levels of adhesion related proteins on the cancer cells, DIF-1 significantly decreased the expression levels of vascular cell adhesion molecule-1 (VCAM-1) on HUVECs by suppression of protein translation via repression of mTORC1-p70 S6 kinase signaling. DIF-1 is expected to be a lead compound for the development of anti-cancer drugs.

Free Research Field

薬理学, 腫瘍学

Academic Significance and Societal Importance of the Research Achievements

手術療法はがん治療の有効な手段であるが、手術によって転移が引き起こされるリスクが懸念されている。DIF-1が脈管内に侵入した循環腫瘍細胞の活性を抑制し、血管内皮細胞への接着を抑制することで、がん転移を防ぐことができれば、周術期のがん標準治療を改革しうる。従来の抗腫瘍薬は、細胞を殺すことで作用するため、有害反応が起こる可能性が高いが、DIF-1は正常細胞に対する影響が少なく、有害反応が少ない化合物であるため、体力が落ちた患者にとっても使用できる有用な治療薬となりうる。